Abstract
Over the past 15 years, a significant increase in new HIV/AIDS diagnoses has been observed in the elderly population. This new epidemiological shift has been attributed to a longer sex life, lifestyle and changes in sexual behavior, poor sexual health education, and misconceptions about the absence of sexually transmitted disease in later life. Although many biomedical and behavioral interventions have proven useful to prevent sexually transmitted infections and HIV, pre-exposure prophylaxis (PrEP) has been shown to be the most successful biomedical intervention to prevent HIV in high-risk individuals. This approach is based on delivering a fixed dose of tenofovir disoproxil fumarate (300 mg), alone or combined with emtricitabine (300/200 mg) daily or on demand, before and after sexual intercourse. Despite the consistent number of clinical trials proving the effectiveness and safety of this strategy, no studies have focused specifically on elderly people. These individuals, who may benefit substantially from (PrEP), are at a higher risk of experiencing side effects secondary to tenofovir exposure. This review critically discusses the efficacy and safety of PrEP in people aged over 50 years and translates the knowledge of tenofovir management in patients with HIV into monitoring and stopping rules to be used in this special population. We provide practical recommendations to properly identify PrEP candidates among older adults. Furthermore, we define correct case management before and during PrEP delivery, and we suggest stopping rules and alternative sexually transmitted infection prevention strategies.
Similar content being viewed by others
References
Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365(6):493–505. https://doi.org/10.1056/NEJMoa1105243.
European AIDS Clinical Society. Guidelines for treatment of HIV-positive adults in Europe. http://www.eacsociety.org/guidelines/eacs-guidelines/eacs-guidelines.html. Accessed 16 Oct 2017.
Wright E, Grulich A, Roy K, et al. Australasian Society for HIV, viral hepatitis and sexual health medicine HIV pre-exposure prophylaxis: clinical guidelines. J Virus Erad. 2017;3(3):168–84.
World Health Organization. Guidance on oral pre-exposure prophylaxis (PrEP) for serodiscordant couples, men and transgender women who have sex with men at high risk of HIV: recommendations for use in the context of demonstration projects. 2012. http://www.who.int/hiv/pub/guidance_prep/en/. Accessed 26 Mar 2018.
Centers for Disease and Control and Prevention. Preexposure prophylaxis for the prevention of HIV infection in the United States: 2014 clinical practice guideline. https://www.cdc.gov/hiv/risk/prep/index.html. Accessed 16 Oct 2017.
Adimora AA, Cole SR, Eron JJ, et al. US black women and human immunodeficiency virus prevention: time for new approaches to clinical trials. Clin Infect Dis. 2017;65(2):324–7.
Smith DK, Pals SL, Herbst JH, et al. Development of a clinical screening index predictive of incident HIV infection among men who have sex with men in the United States. J Acquir Immune Defic Syndr. 2012;60:421–7.
Kesler MA, Kaul R, Myers T, et al. Perceived HIV risk, actual sexual HIV risk and willingness to take pre-exposure prophylaxis among men who have sex with men in Toronto, Canada. AIDS Care. 2016;28(11):1378–85. https://doi.org/10.1080/09540121.2016.1178703.
Wilton J, Mishra S, Tan DHS, et al. Considerations for using the HIRI-MSM screening tool to identify MSM who would benefit most from PrEP. J Acquir Immune Defic Syndr. 2017;76(2):e58–61. https://doi.org/10.1097/QAI.0000000000001472.
Derdelinckx I, Wainberg MA, Lange JM, et al. Criteria for drugs used in pre-exposure prophylaxis trials against HIV infection. PLoS Med. 2006;3:e454.
Fonsart J, Saragosti S, Taouk M, et al. Single-dose pharmacokinetics and pharmacodynamics of oral tenofovir and emtricitabine in blood, saliva and rectal tissue: a sub-study of the ANRS IPERGAY trial. J Antimicrob Chemother. 2017;72(2):478–85.
Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363(27):2587–99.
Molina JM, Capitant C, Spire B, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med. 2015;373:2237–46. https://doi.org/10.1056/NEJMoa1506273.
Gunawardana M, Remedios-Chan M, Miller CS, et al. Pharmacokinetics of long-acting tenofovir alafenamide (GS-7340) subdermal implant for HIV prophylaxis. Antimicrob Agents Chemother. 2015;59(7):3913–9. https://doi.org/10.1128/AAC.00656-15.
Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367(5):399–410.
McCormack S, Dunn DT, Desai M, et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet. 2016;387:53–60.
Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection among people who inject drugs in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2013;381(9883):2083–90. https://doi.org/10.1016/S0140-6736(13)61127-7.
Yombi JC, Pozniak A, Boffito M, et al. Antiretrovirals and the kidney in current clinical practice: renal pharmacokinetics, alterations of renal function and renal toxicity. AIDS. 2014;28(5):621–32. https://doi.org/10.1097/QAD.0000000000000103.
Guaraldi G, Orlando G, Zona S, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis. 2011;53(11):1120–6. https://doi.org/10.1093/cid/cir627.
Tavoschi L, Gomes Dias J, Pharris A, EU/EEA HIV Surveillance Network. New HIV diagnoses among adults aged 50 years or older in 31 European countries, 2004–15: an analysis of surveillance data. Lancet HIV. 2017;4(11):e514–21. https://doi.org/10.1016/s2352-3018(17)30155-8.
Small LFF. What older adults know about HIV/AIDS: lessons from an HIV/AIDS education program. Educ Gerontol. 2009;36(1):26–45. https://doi.org/10.1080/03601270903058317.
Chen Y, Bussell AS, Shen Z, et al. Declining inconsistent condom use but increasing HIV and syphilis prevalence among older male clients of female sex workers: analysis from sentinel surveillance sites (2010–2015), Guangxi, China. Med (Baltimore). 2016;95(22):e3726. https://doi.org/10.1097/MD.0000000000003726.
Marrazzo JM, Ramjee G, Richardson BA, et al. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2015;372:509–18. https://doi.org/10.1056/NEJMoa1402269.
Grohskopf LA, Chillag KL, Gvetadze R, et al. Randomized trial of clinical safety of daily oral tenofovir disoproxil fumarate among HIV-uninfected men who have sex with men in the United States. J Acquir Immune Defic Syndr. 2013;64(1):79–86. https://doi.org/10.1097/QAI.0b013e31828ece33.
Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012;367(5):423–34.
Anderson PL, Glidden DV, Liu A, et al. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med. 2012;4(151):151ra125.
Anderson PL, Liu AY, Castillo-Mancilla JR, et al. Intracellular tenofovir-diphosphate and emtricitabine-triphosphate in dried blood spots following directly observed therapy. Antimicrob Agents Chemother. 2017;62(1):e01710–7.
Patterson KB, Prince HA, Kraft E, Jenkins AJ, Shaheen NJ, Rooney JF, Cohen MS, Kashuba AD. Penetration of tenofovir and emtricitabine in mucosal tissues: implications for prevention of HIV-1 transmission. Sci Transl Med. 2011;3(112):1124. https://doi.org/10.1126/scitranslmed.3003174.
Seifert SM, Castillo-Mancilla JR, Erlandson K, et al. Brief report: adherence biomarker measurements in older and younger HIV-infected adults receiving tenofovir-based therapy. J Acquir Immune Defic Syndr. 2018;77(3):295–8.
Nelson MR, Katlama C, Montaner JS, et al. The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years. AIDS. 2007;21(10):1273–81.
Izzedine H, Hulot JS, Vittecoq D, et al. Long-term renal safety of tenofovir disoproxil fumarate in antiretroviral-naïve HIV-1-infected patients: data from a double-blind randomized active-controlled multicentre study. Nephrol Dial Transplant. 2005;20:743–6. https://doi.org/10.1093/ndt/gfh658.
Tang EC, Vittinghoff E, Anderson PL, et al. Changes in kidney function associated with daily tenofovir disoproxil fumarate/emtricitabine for HIV preexposure prophylaxis use in the United States Demonstration Project. J Acquir Immun Defic Syndr. 2018;77(2):193–8.
Mugwanya KK, Wyatt C, Celum C, et al. Reversibility of glomerular renal function decline in HIV-uninfected men and women discontinuing emtricitabine-tenofovir disoproxil fumarate pre-exposure prophylaxis. J Acquir Immune Defic Syndr. 2016;71:374–80.
McComsey GA, Tebas P, Shane E, et al. Bone disease in HIV infection: a practical review and recommendations for HIV care providers. Clin Infect Dis. 2010;51(8):937–46.
Bedimo R, Maalouf NM, Zhang S, et al. Osteoporotic fracture risk associated with cumulative exposure to tenofovir and other antiretroviral agents. AIDS. 2012;26:825–31.
Mirembe BG, Kelly CW, Mgodi N, et al. Bone mineral density changes among young, healthy African women receiving oral tenofovir for HIV preexposure prophylaxis. J Acquir Immune Defic Syndr. 2016;71:287–94.
Glidden DV, Mulligan K, McMahan V. Brief report: recovery of bone mineral density after discontinuation of tenofovir-based HIV pre-exposure prophylaxis. J Acquir Immune Defic Syndr. 2017;76(2):177–82. https://doi.org/10.1097/QAI.0000000000001475.
Liu AY, Vittinghoff E, Sellmeyer DE, et al. Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco. PloS One. 2011;6(8):e23688. https://doi.org/10.21371/journal.pone.0023688.
Calmy A, Hirschel B, Cooper DA, et al. A new era of antiretroviral drug toxicity. Antivir Ther. 2009;14:165–79.
Anderson PL, Kiser JJ, Gardner EM, Rower JE, Meditz A, Grant MR. Pharmacological considerations for tenofovir and emtricitabine to prevent HIV infection. J Antimicrob Chemother. 2011;66:240–50. https://doi.org/10.1093/jac/dkq447.
Gandhi M, Glidden DV, Mayer K, et al. Association of age, baseline kidney function, and medication exposure with declines in creatinine clearance on pre-exposure prophylaxis: an observational cohort study. Lancet HIV. 2016;3(11):e521–8. https://doi.org/10.1016/S2352-3018(16)30153-9.
Glidden DV, Mulligan K, McMahan V, et al. Metabolic effects of pre-exposure prophylaxis with co-formulated tenofovir disoproxal fumarate and emtricitabine. Clin Infect Dis. 2018. https://doi.org/10.1093/cid/ciy083 (Epub ahead of print).
Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012;367(5):411–22.
Acknowledgements
Both authors are responsible for the intellectual content, critical revisions, and approval of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
No funding was received for the preparation of this article.
Conflict of interest
Giovanni Guaraldi and Iacopo Franconi have no conflicts of interest directly relevant to the content of this article.
Rights and permissions
About this article
Cite this article
Franconi, I., Guaraldi, G. Pre-exposure Prophylaxis for HIV Infection in the Older Patient: What can be Recommended?. Drugs Aging 35, 485–491 (2018). https://doi.org/10.1007/s40266-018-0553-3
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40266-018-0553-3